The object of this research program is to carry out biophysical and biochemical studies on the nucleic acids to understand the mechanism of their action in biological systems. The central part of this program is the determination of the structure of protein-nucleic acid complexes to understand the manner in which nucleic acid conformation is modified through its interaction with protein. The major technique used in this work is X-ray diffraction studies. We now have crystals of complexes containing the single-stranded DNA binding protein from fd bacteriophage with oligo-nucleotides of DNA. In addition, we are also working on the structure of a complex containing the E. coli Hu protein and double helical fragments of DNA. A number of other protein-nucleic acid complexes are also being studied with a view toward crystallizing them in the complex form and toward their suitability for crystallographic analysis. Crystallographic studies will also be carried out on other nucleic acid components, including oligonucleotides, to study their natural conformation as well as the manner in which their conformation is modified by interaction with other molecules, including peptides. This includes the structure of DNA fragments of defined sequence. The central goal of this research program is to try to understand the general rules by which proteins and nucleic acids interact, using sequence-specific interactions as well as interactions which are not sequence specific. In addition, considerable effort is focused on the manner in which conformational changes in the nucleic acids are introduced through their interactions with proteins. (F)